The circumsporozoite(CS) protein of Plasmodium falciparum has been the focus of an intensive effort to develop and antisporozoite malaria vaccine. However, in recent human trials, malaria vaccines based on the immunodominant CS protein repeat showed a lack of immunogenicity with little or no boosting and poor protection. Therefore, alternative strategies to identify additional sporozoite and exoerythrocytic stage antigens as potential vaccine candidates are necessary. Immunization with P.falciparum sporozoites protects mice to P.berghei sporozoite challenge. A 42/54kD protein (designated CSP-2) present in the sporozoites of both species appears to mediate the protective response because passively transferred polyclonal and monoclonal antibodies which recognize this antigen prevent P. berghei infection. CSP-2 is found on the surface of sporozoites and associated with the parasitophorous vacuole of liver stage parasites. The gene encoding P.falciparum CSP-2 has been cloned. Sequence analysis shows that CSP-2 is an asparagine rich protein unrelated to other known malaria antigens. Cloning of the P.berghei CSP-2 gene is proposed based on crosshybridzation of the P.falciparum gene with specific P.berghei genomic restriction fragments. DNA sequence analysis coupled to biosynthesis studies and immunogenicity/protection trials in mice are proposed to fully dissect the structural characteristics of P.berghei CSP-2 relevant to the protective immune response (ie B- and T-cell epitopes, proteolytic processing, glycosylation, membrane attachment) . The overall objective of the proposed research is to define the role of CSP-2 antigen in protection against sporozoite induced murine malaria as a model for P.falciparum CSP-2 development as a human anti-malarial vaccine.